A 70-year-old man is diagnosed with a pulmonary nocardia infection. Medical conditions include hypertension and diet-controlled type 2 diabetes mellitus. Therapy is started with trimethoprim-sulfamethoxazole for a planned duration of 3-6 months. This patient is at greatest risk for which of the following drug-induced adverse effects?

Question

A 70-year-old man is diagnosed with a pulmonary nocardia infection.  Medical conditions include hypertension and diet-controlled type 2 diabetes mellitus.  Therapy is started with trimethoprim-sulfamethoxazole for a planned duration of 3-6 months.  This patient is at greatest risk for which of the following drug-induced adverse effects?

Quizplus · Accepted Answer

Trimethoprim-sulfamethoxazole (TMP-SMX) is a combination of 2 bacteriostatic antibiotics that act synergistically to inhibit bacterial tetrahydrofolate formation, resulting in bactericidal activity. It has a broad spectrum of activity against many aerobic gram-positive and gram-negative bacteria and is commonly used for urinary tract infections, Pneumocystis jiroveci pneumonia, and Nocardia infections. Common adverse effects of TMP-SMX include rash, nausea and vomiting, and folate deficiency (with prolonged use). In addition, hyperkalemia is a common adverse effect that can occur, regardless of dose. Similar to the actions of amiloride (a potassium-sparing diuretic), trimethoprim blocks the epithelial sodium channel in the distal tubule and collecting duct. This reduces transepithelial voltage and impairs sodium-potassium exchange, leading to reduced potassium excretion and hyperkalemia. This effect is often magnified in the elderly population, those with renal failure, or those given other potassium-sparing diuretics (eg, spironolactone, amiloride), ACE inhibitors (eg, lisinopril), or angiotensin receptor blockers (eg, losartan). This patient with hypertension and diabetes may be receiving an ACE inhibitor, which further increases his risk of developing hyperkalemia. (Choice A) Tetracyclines (eg, doxycycline, minocycline) and clindamycin are associated with esophagitis due to their low pH and irritant effects on the distal esophagus. (Choice B) Aminoglycosides (eg, gentamycin, tobramycin) have broad-spectrum activity against aerobic gram-negative organisms and are most often used in severe gram-negative infections (eg, intraabdominal infections, osteomyelitis). These medications are associated with ototoxicity and may lead to tinnitus and hearing loss. (Choice D) Nitrofurantoin has activity against many gram-positive and gram-negative urinary tract pathogens and is used for both acute treatment of urinary tract infections and long-term prophylaxis in patients with recurrent cystitis. It is associated with pneumonitis and pulmonary fibrosis. (Choice E) Fluoroquinolones (eg, levofloxacin, ciprofloxacin) have activity against aerobic gram-negative rods and many respiratory pathogens. They are commonly used to treat pneumonia, pseudomonal infections, and urinary tract infections. These medications are associated with tendinopathy, including tendon rupture. Educational objective: Hyperkalemia is a common adverse effect of trimethoprim-sulfamethoxazole due to the trimethoprim-induced blockade of the sodium channels in the collecting duct, which prevents sodium-potassium exchange and reduces renal excretion of potassium (similar to the action of amiloride). This effect is often magnified in the elderly population, those with renal failure, or those given other potassium-sparing diuretics, ACE inhibitors, or angiotensin receptor blockers.

A 70-Year-Old Man Is Diagnosed with a Pulmonary Nocardia Infection